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We report in vivo development of cefiderocol (FDC) resistance among four sequential Pseudomonas aeruginosa clinical isolates ST244 recovered from a single patient, without exposure to FDC, which raises concern about the effectiveness of this novel drug. The first recovered P. aeruginosa isolate (P-01) was susceptible to FDC (2 μg/mL), albeit this MIC value was higher than that of a wild-type P. aeruginosa (0.12–0.25 μg/ml). The subsequent isolated strains (P-02, P-03, P-04) displayed increasing levels of FDC MICs (8, 16, and 64 μg/ml, respectively). Those isolates also showed variable and gradual increasing levels of resistance to most β-lactams tested in this study. Surprisingly, no acquired β-lactamase was identified in any of those isolates. Whole-genome sequence analysis suggested that this resistance was driven by multifactorial mechanisms including mutational changes in iron transporter proteins associated with FDC uptake, ampC gene overproduction, and mexAB-oprM overexpression. These findings highlight that a susceptibility testing to FDC must be performed prior to any prescription.

Metastasis and drug resistance are major problems in cancer chemotherapy. The purpose of this work was to analyze the molecular mechanisms underlying the invasive potential of drug-resistant colon carcinoma cells. Cellular models included the parental HT-29 cell line and its drug-resistant derivatives selected after chronic treatment with either 5-fluorouracil, methotrexate, doxorubicin, or oxaliplatin. Drug-resistant invasive cells were compared with noninvasive cells using cDNA microarray, quantitative reverse transcription-PCR, flow cytometry, immunoblots, and ELISA. Functional and cellular signaling analyses were undertaken using pharmacologic inhibitors, function-blocking antibodies, and silencing by retrovirus-mediated RNA interference. 5-Fluorouracil– and methotrexate-resistant HT-29 cells expressing an invasive phenotype in collagen type I and a metastatic behavior in immunodeficient mice exhibited high expression of the chemokine receptor CXCR4. Macrophage migration-inhibitory factor (MIF) was identified as the critical autocrine CXCR4 ligand promoting invasion in drug-resistant colon carcinoma HT-29 cells. Silencing of CXCR4 and impairing the MIF-CXCR4 signaling pathways by ISO-1, pAb FL-115, AMD-3100, monoclonal antibody 12G5, and BIM-46187 abolished this aggressive phenotype. Induction of CXCR4 was associated with the upregulation of two genes encoding transcription factors previously shown to control CXCR4 expression (HIF-2α and ASCL2) and maintenance of intestinal stem cells (ASCL2). Enhanced CXCR4 expression was detected in liver metastases resected from patients with colon cancer treated by the standard FOLFOX regimen. Combination therapies targeting the CXCR4-MIF axis could potentially counteract the emergence of the invasive metastatic behavior in clonal derivatives of drug-resistant colon cancer cells. Cancer Res; 70(11); 4644–54. ©2010 AACR.

Supplementary Methods, Figure Legends 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Supplementary Figure 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Summary Colonization resistance by gut microbiota is a fundamental phenomenon in infection prevention and control. Hospitalized patients may be exposed to multi-drug-resistant bacteria when hand hygiene compliance among healthcare workers is not adequate. An additional layer of defence is provided by the healthy gut microbiota, which helps clear the exogenous bacteria and acts as a safety net when hand hygiene procedures are not followed. This narrative review focuses on the role of the gut microbiota in colonization resistance against multi-drug-resistant bacteria, and its implications for infection control. The review discusses the underlying mechanisms of colonization resistance (direct or indirect), the concept of resilience of the gut microbiota, the link between the antimicrobial spectrum and gut dysbiosis, and possible therapeutic strategies. Antimicrobial stewardship is crucial to maximize the effects of colonization resistance. Avoiding unnecessary antimicrobial therapy, shortening the antimicrobial duration as much as possible, and favouring antibiotics with low anti-anaerobe activity may decrease the acquisition and expansion of multi-drug-resistant bacteria. Even after antimicrobial therapy, the resilience of the gut microbiota often occurs spontaneously. Spontaneous resilience explains the existence of a window of opportunity for colonization of multi-drug-resistant bacteria during or just after antimicrobial therapy. Strategies favouring resilience of the gut microbiota, such as high-fibre diets or precision probiotics, should be evaluated.

Resume Chlamydia trachomatis (CT) est l’infection bacterienne sexuellement transmissible la plus repandue mondialement. Elle est souvent asymptomatique et touche principalement la femme jeune, avec des repercussions potentielles a long terme (maladie inflammatoire pelvienne, infertilite tubaire, complications obstetricales). Le retentissement sur la fertilite masculine est discute. Les modalites de depistage et l’utilisation des antibiotiques ont recemment ete reevaluees du fait des phenomenes de resistance et de l’impact negatif sur le microbiote urogenital. La serologie CT positive peut etre le temoin d’une pathologie tuboperitoneale, pouvant passer inapercue a l’hysterosalpingographie. De nouvelles recherches portant sur les single-nucleotide polymorphisms (SNPs) tentent d’etablir un profil de patiente plus a risque de sequelle tubaire infectieuse a CT. La seropositivite vis-a-vis de CT est egalement associee a une diminution du taux de grossesse spontanee et constitue un facteur predictif de complications obstetricales.

Bacteria of the genus

Carbapenemase-producing Enterobacterales (CPE) are spreading rapidly in hospital settings. Asymptomatic CPE gut colonisation may be associated with dysbiosis and gut-lung axis alterations, which could impact lung infection outcomes. In this study, in male C57BL/6JRj mice colonised by CPE, we characterise the resulting gut dysbiosis, and analyse the lung immune responses and outcomes of subsequent Pseudomonas aeruginosa lung infection. Asymptomatic gut colonisation by CPE leads to a specific gut dysbiosis and increases the severity of P. aeruginosa lung infection through lower numbers of alveolar macrophages and conventional dendritic cells. CPE-associated dysbiosis is characterised by a near disappearance of the Muribaculaceae family and lower levels of short-chain fatty acids. Faecal microbiota transplantation restores immune responses and outcomes of lung infection outcomes, demonstrating the involvement of CPE colonisation-induced gut dysbiosis in altering the immune gut-lung axis, possibly mediated by microbial metabolites such as short-chain fatty acids.

Resume L’endometrite du post-partum est frequente et represente 2 % des infections du post-partum dans les pays a bon niveau socioeconomique. En France, 2,3 % des deces sont imputes aux infections puerperales. Le facteur de risque le plus important est l’accouchement par cesarienne, d’autant plus lorsque celle-ci est effectuee apres le debut du travail. Les bacteries du microbiote vaginal sont associees a l’endometrite du post-partum. Les signes d’appel sont l’apparition de douleurs abdominopelviennes, une hyperthermie, des lochies anormales. Le diagnostic est clinique, confirme par une douleur a la mobilisation uterine. L’antibiotherapie probabiliste de premiere intention est l’amoxicilline–acide clavulanique, 3 a 6 grammes par jour selon le poids par voie intraveineuse ou per os. En cas de contre-indication aux penicillines (anaphylaxie par exemple), l’association clindamycine 600 mg × 4/j plus gentamicine 5 mg/kg × 1/j sera utilisee, elle doit relever d’un avis specialise en cas d’allaitement maternel. Le traitement est poursuivi jusqu’a l’obtention de 48 heures d’apyrexie et la disparition des douleurs provoquees. En cas de persistance de la fievre et/ou des douleurs pelviennes apres 72 heures d’antibiotherapie, une imagerie pelvienne devra etre realisee pour rechercher une retention placentaire, une thrombophlebite pelvienne septique, un abces profond ou tout autre complication chirurgicale, et eliminer les diagnostics differentiels. Il est important de souligner les difficultes d’interpretation des images endo-uterines en echographie. Une heparinotherapie a posologie hypocoagulante doit etre debutee en cas de thrombophlebite pelvienne septique pour une duree de 6 semaines, ou plus s’il existe des complications a type d’embols ou des facteurs de risque thrombotique. Concernant la prevention, lors d’une cesarienne, un badigeonnage vaginal avec de la polividone-iodee ou de la chlorhexidine est recommande avant la cesarienne si possible, et la delivrance du placenta doit etre spontanee.

Objectives Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of β-lactamases and Enterobacterales’ genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs. Materials and methods In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates’ ST and their type of β-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed. Results All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant β-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54). Conclusions Despite the frequent association of ESBL genes with inhibitor-resistant β-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children.

Answer: b. Extragenital M. hominis infections classically occur in patients who present with hypogammaglobulinemia, have received a solid-organ transplant, or have recently undergone surgery (postoperative infections). There is no literature precedent for an association between neutropenia, obesity

A 55-year-old woman with an unexplored 1-month history of rectal bleeding presented to the emergency department with abdominal pain, chills, and fever. The patient had received rituximab, a monoclonal antibody targeting the CD20 antigen expressed on B cells, for rheumatoid arthritis. An abdominal

International audience; A recently developed, automated blood culture system and medium improve the timeto-positivity (TTP) for bacteremia. However, there have thus far been no genus-level analyses using this novel system. We evaluated and compared the changes in blood culture TTP between two systems: BacT/Alert 3D with a blood culture medium containing activated charcoal versus the more recent BacT/Alert Virtuo with a blood culture medium containing polymeric beads. This before-and-after study included blood cultures collected between July 2010 and April 2014 (3D, activated charcoal) and between July 2015 and April 2018 (Virtuo, polymeric beads). A total of 554,732 blood cultures were included, 267,935 (48.30%) during the first period and 286,797 (51.70%) during the second period. Overall, 55,611 (10.02%) tested positive for at least one microorganism. The incubation of the blood culture medium in the Virtuo system was associated with reduced TTP for the most prevalent bacteria, those representing 91.72% (n=51,006) of all the positive blood cultures. The median TTP was reduced by 0.99 hours for Staphylococcus, Enterococcus, Streptococcus, Pseudomonadales, and most of the genera within the order Enterobacterales (except the family Morganellaceae). However, strictly anaerobic bacteria belonging to the genus Bacteroides, representing 0.85% (n=474) of all positive blood cultures, were detected 4.53 hours later using the Virtuo system. Virtuo was associated with a shorter TTP for most bacteria, but this improvement was heterogeneous to the genus level.

Objective Low-birthweight infants admitted to neonatal intensive care units are at high risk of hospital-acquired infections by opportunistic pathogens. The gut microbiota of preterm neonates lacks commensal bacteria providing a barrier against pathogens. We report a case of bacteremia due to Kosakonia cowanii in a preterm neonate. Case Report A female baby of 680 g was delivered through a cesarean-section at 28 weeks of gestation due to intrauterine growth retardation and fetal rhythm abnormalities. On day 27, two blood cultures grew gram-negative bacilli in a context of functional ileus. No reliable identification could be obtained using matrix assisted laser desorption ionization-time of flight, biochemical reactions with the VITEK 2 GN ID card, or 16S rDNA sequencing. K. cowanii was finally identified by gyrB sequencing. The source of infection may have been either the central venous catheter or translocation from the gut microbiota. Evolution was favorable after 14 days of cefepime (combined with amikacin for 5 days) and central venous catheter removal. Conclusion K. cowanii is a member of the Enterobacteriaceae family that was recently reclassified from the Enterobacter genus. Human infections due to K. cowanii are scarce and have mainly been associated with traumatic inoculation from plants or transient gut colonization. K. cowanii may be an underestimated opportunistic pathogen in susceptible populations such as preterm neonates.

Graphical abstract Characteristics of host-microbiota interactions in asthmatic children favor asthma attacks and may allow to define asthma endotypes. This knowledge offers promising perspectives to treat asthmatic children using precision medicine, Exacerbations are a main characteristic of asthma. In childhood, the risk is increasing with severity. Exacerbations are a strong phenotypic marker, particularly of severe and therapy-resistant asthma. These early-life events may influence the evolution and be involved in lung function decline. In children, asthma attacks are facilitated by exposure to allergens and pollutants, but are mainly triggered by microbial agents. Multiple studies have assessed immune responses to viruses, and to a lesser extend bacteria, during asthma exacerbation. Research has identified impairment of innate immune responses in children, related to altered pathogen recognition, interferon release, or anti-viral response. Influence of this host-microbiota dialog on the adaptive immune response may be crucial, leading to the development of biased T helper (Th)2 inflammation. These dynamic interactions may impact the presentations of asthma attacks, and have long-term consequences. The aim of this review is to synthesize studies exploring immune mechanisms impairment against viruses and bacteria promoting asthma attacks in children. The potential influence of the nature of infectious agents and/or preexisting microbiota on the development of exacerbation is also addressed. We then discuss our understanding of how these diverse host-microbiota interactions in children may account for the heterogeneity of endotypes and clinical presentations. Finally, improving the knowledge of the pathophysiological processes induced by infections has led to offer new opportunities for the development of preventive or curative therapeutics for acute asthma. A better definition of asthma endotypes associated with precision medicine might lead to substantial progress in the management of severe childhood asthma.

BackgroundGut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult.Here we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection.MethodsC57BL6 mice were administered 7 days oral vancomycin-colistin, modulated or not by fecal microbial transplant or exogenous hematopoietic cytokine, Fms-related tyrosine kinase 3 ligand (Flt3-Ligand), followed by intranasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow.ResultsVancomycin-colistin administration induces widespread cellular immunosuppression in both lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. ConclusionsThese results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis.

International audience; Clostridium spp. are recovered from 25% of the blood culture positive with anaerobes. However, the clinical relevance of Clostridium bacteremia has been controverted in the literature, particularly for C. perfringens. We aimed to evaluate the clinical relevance of Clostridium bacteremia, either due to C. perfringens or other Clostridium species, and to identify the risk factors of mortality in these patients. A retrospective cohort study was conducted from January 2010 to April 2018. All the patients with at least one blood culture positive with any Clostridium species were included. Eighty-one patients with a least one blood culture positive with any Clostridium species were included. Seventy patients (86.4%) fulfilled the criteria for clinically relevant bacteremia. Bacteremia due to C. perfringens tended to be less clinically relevant than other Clostridium species but this was not statistically significant (76% vs 91.2%, P = 0.09). In case of clinically relevant bacteremia, the 30-day mortality rate was 31.4%. In multivariate analysis, adequate empiric antimicrobial therapy was significantly associated with survival (P = 0.03). In conclusion, bacteremia due to C. perfringens or other Clostridium species is usually clinically relevant. This finding was also supported by an improved survival at 30 days when adequate empiric antimicrobial therapy was administered.

Background Preschool asthma/recurrent wheeze is a heterogeneous condition. Different clinical phenotypes have been described, including episodic viral wheeze (EVW), severe intermittent wheeze (SIW), and multiple-trigger wheeze (MTW). Objective To compare clinical, viral, and inflammatory/immune profiling at exacerbation between MTW, SIW, and EVW phenotypes. Methods Multicenter, prospective, observational cohort (VIRASTHMA-2). Children (1-5 years) with preschool asthma were enrolled during hospitalization for a severe exacerbation. History and anamnestic data, plasma, and nasal samples were collected at exacerbation (T1) and at steady state, 8 weeks later (T2), and sputum samples were collected at T1. Results A total of 147 children were enrolled, 37 (25%) had SIW, 18 (12.2%) EVW, and 92 (63%) MTW. They were atopic (47%), exposed to mold (22%) and cigarette smoke (50%), and prone to exacerbations (≥2 in the previous year in 70%). At exacerbation, at least one virus was isolated in 94% and rhinovirus in 75%, with no difference between phenotypes. Children with MTW and SIW phenotypes displayed lower plasma concentrations of IFN-γ (P = .002), IL-5 (P = .020), TNF-α (P = .038), IL-10 (P = .002), IFN-β (P = .036), and CXCL10 (P = .006) and lower levels of IFN-γ (P = .047) in sputum at exacerbation than children with EVW. At T2, they also displayed lower plasma levels of IFN-γ (P = .045) and CXCL10 (P = .013). Conclusion Among preschool asthmatic children, MTW and SIW, prone to exacerbations, display lower systemic levels of Th1, Th2 cytokines, pro- and anti-inflammatory cytokines, and antiviral responses during severe virus-induced exacerbation.

International audience; This study aimed to analyse the frequency of occurrence of spontaneous decolonization in intensive care unit patients colonized by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in order to assess the added value of continuing weekly ESBL-E rectal carriage screening in these patients. In total, 49,468 weekly rectal screening samples taken from 20,846 patients over 12 years were included. Among the 4280 ESBL-E carriers, only 109 patients (2.5%) could be considered decolonized at the end of their hospitalization with at least three consecutive negative samples. Overall, 7957 samples (16.1%) were requested for patients already identified as ESBL-E carriers. Avoiding unnecessary weekly screening following positive ESBL-E colonization results could decrease nursing and laboratory work loads.

Objective To evaluate clinical practices for ESBL-producing urinary tract infection (UTI) in France. Methods We performed an observational, retrospective, cross-sectional, hospital-based study in 22 pediatric departments of university or secondary care hospitals. We collected data of the last five patients presenting with ESBL-producing UTI in 2012 and the physicians’ therapeutic approach to two case vignettes of acute non-septic ESBL-producing pyelonephritis (7-month-old girl) and cystitis (30-month-old girl). The adequacy of the therapeutic decision was analyzed by a panel of independent infectious disease experts. Results A total of 80 case patients of ESBL-producing UTI were collected: 54 with acute pyelonephritis (mean age: 28 months, female: 66%), of whom 98% received an intravenous ESBL-adapted antibiotic treatment and 55% a two-drug antibiotic therapy. Carbapenems were used in 56% of cases and aminoglycosides in 36%. Of the 26 cystitis patients (mean age: 5 years, female: 73%), 85% were treated with antibiotics, including three intravenously (carbapenems = 2). For the case vignettes, physicians (n = 85) would have treated the pyelonephritis patient with carbapenems (76%) and/or aminoglycosides (68%); 71% would have used a two-drug antibiotic treatment. The cystitis patient would have been treated intravenously by 29% of physicians; 8% would have used a two-drug antibiotic treatment, 16% would have prescribed carbapenems, and 11% aminoglycosides. Antibiotic treatments were deemed appropriate in 37% of cases. Conclusions Antimicrobial treatment for ESBL-producing UTI greatly varies, and carbapenems are excessively prescribed. Specific guidelines for ESBL infections are required.

While NLRC4-dependent sensing of intracellular Gram-negative pathogens such as Salmonella enterica serovar typhimurium is a beneficial host response, NLRC4-dependent sensing of the Pseudomonas aeruginosa type 3 secretion system (T3SS) has been shown to be involved in pathogenicity. In mice, different pathogen-associated microbial patterns are sensed by the combination of the NLRC4-inflammasome with different neuronal apoptosis inhibitory proteins (NAIPs). NAIP2 is involved in sensing PscI, an inner-rod protein of the P. aeruginosa T3SS. Surprisingly, only a single human NAIP (hNAIP) has been found. Moreover, there is no description of hNAIP-NLRC4 inflammasome recognition of T3SS inner-rod proteins in humans. Here, we show that the P. aeruginosa T3SS inner-rod protein PscI and needle protein PscF are both sensed by the hNAIP-NLRC4 inflammasome in human macrophages and PBMCs from healthy donors, allowing caspase-1 and IL-1β maturation and resulting in a robust inflammatory response. TLR4 and TLR2 are involved in redundantly sensing these two T3SS components.

Objective: Describe the microbiological status during a severe asthma exacerbation and at steady state in preschool children ( Methods: Multicenter prospective study (Hauts-de-France, France). 147 asthmatic children were included during an hospitalization for a severe exacerbation (2015-2018). Phenotype, atopic status, viral status (PCR, nasal swab sample), bacteriological status (culture, induced sputum) were assessed during the exacerbation and at steady state, 8 weeks later. Results: We observed a seasonal distribution of the inclusions (figure). During the exacerbation, a virus was identified in 94% (V+); rhinovirus (RV) in 74% (R+), more frequently in June (95%) and September (82%) (p Conclusion: We confirm a high prevalence of RV infection during asthma exacerbations, frequently associated with bacteria. We now aim at exploring the host immune innate responses to these microorganisms.

BACKGROUND Pneumococcal meningitis (PM) is a serious disease that can rarely recur at a later time after the initial episode. METHODS A retrospective multicenter case-control study was conducted with data for children 18 years of age or younger obtained from the National Observatory of Bacterial Meningitis in Children between January 2001 and September 2015. Cases were all patients with RPM. Each case was matched with 2 randomized controls with a single PM episode in the year of the first episode of PM in the case and born the same year. Case and control data were compared. RESULTS Among the 1634 PM episodes in children 18 years of age or younger, 24 (1.5%) children had RPM. RPM cases were significantly less frequent than single PM cases in winter (27% vs. 48%; P=0.03) and showed significantly less concomitant ear, nose and throat infections when considering the first episode (30% vs. 56%, P = 0.04) and all episodes (28% vs. 56%, P < 0.01). Cerebrospinal fluid leakage was frequent in RPM cases versus controls (83% vs. 10%, P < 0.01), including 25% discovered after the third PM episode. Immune deficiency was absent in cases and present in 15% of controls. Cases and controls did not differ in death rate or neurologic outcome. CONCLUSIONS RPM is rare in children. Cerebrospinal fluid leakage must be considered.

International audience; Clostridium ventriculi (formerly Sarcina ventriculi) is a Gram-positive, obligate anaerobic coccus. Human infections due to this bacterium have rarely been reported, its involvement in the development of gastric ulcers and perforation has been suggested. We present a case of bacteremia due to C. ventriculi following acute colonic pseudo-obstruction.

While antibiotic use is a risk factor of carbapenemase-producing Enterobacteriaceae (CPE) acquisition, the importance of timing of antibiotic administration relative to CPE exposure remains unclear. In a murine model of gut colonization by New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae , a single injection of clindamycin within at most 1 week before or after CPE exposure induced colonization persisting up to 100 days.

International audience; Tetraphenylethylene (TPE) is fluorescent through aggregation induced emission (AIE) in water. Herein, TPE was used as the core of glycoclusters that target the bacterial lectins LecA and LecB of Pseudomonas aeruginosa. Synthesis of these TPE-based glycoclusters was accomplished by using azide-alkyne "click" chemistry. The AIE properties of the resulting glycoclusters could be readily verified, but imaging could not be pursued due to the overlap of the fluorescence signals from cells and bacteria. Nonetheless, the glycoclusters displayed nanomolar affinities toward LecA and LecB. Further evaluation in a cell-based anti-adhesive assay highlighted a limited decrease in adhesion (20%) for the fucosylated glycocluster. This confirmed that these TPE-based glycoclusters are indeed LecA and LecB high-affinity ligands. Nevertheless, the hypotheses involving their application in imaging or anti-adhesive therapy could not be verified.

Carbapenemase-producing Klebsiella pneumoniae represents an emerging public health issue. Here, we present the draft whole-genome sequences of K. pneumoniae clinical strains KPL0.1 (OXA-48 carbapenemase) and KPL0.2 (NDM-1 carbapenemase)., Carbapenemase-producing Klebsiella pneumoniae represents an emerging public health issue. Here, we present the draft whole-genome sequences of K. pneumoniae clinical strains KPL0.1 (OXA-48 carbapenemase) and KPL0.2 (NDM-1 carbapenemase). These genome sequences should help in investigating pathophysiological mechanisms of digestive colonization or infection with these highly resistant bacteria.

Background Although vaccination of pregnant women against influenza is recommended, the vaccination rate remains low. We conducted a study to identify determinants of influenza vaccination uptake in pregnancy in order to identify strategies to improve seasonal influenza vaccination rates. Methods Prospective observational hospital-based study in the French hospital performing the highest number of deliveries, located in the city of Lille, among all women who had given birth during the 2014–2015 influenza season. Data were collected through a self-completed questionnaire and from medical files. The vaccination uptake was self-reported. Determinants of vaccination uptake were identified using logistic regression analysis. Results Of the 2045 women included in the study, 35.5% reported that they had been vaccinated against influenza during their pregnancy. The principal factors significantly associated with greater vaccination uptake were previous influenza vaccination (50.9% vs 20.2%, OR 4.1, 95% CI 3.1–5.5), nulliparity (41.0% vs 31.3%, OR 2.5, 95% CI 1.7–3.7), history of preterm delivery

International audience; Background: Preterm delivery during pregnancy (

The export of bacterial toxins across the bacterial envelope requires the assembly of complex, membrane-embedded protein architectures. Pseudomonas aeruginosa employs type III secretion (T3S) injectisome to translocate exotoxins directly into the cytoplasm of a target eukaryotic cell. This multi-protein channel crosses two bacterial membranes and extends further as a needle through which the proteins travel. We show in this work that PscI, proposed to form the T3S system (T3SS) inner rod, possesses intrinsic properties to polymerize into flexible and regularly twisted fibrils and activates IL-1β production in mouse bone marrow macrophages in vitro. We also found that point mutations within C-terminal amphipathic helix of PscI alter needle assembly in vitro and T3SS function in cell infection assays, suggesting that this region is essential for an efficient needle assembly. The overexpression of PscF partially compensates for the absence of the inner rod in PscI-deficient mutant by forming a secretion-proficient injectisome. All together, we propose that the polymerized PscI in P. aeruginosa optimizes the injectisome function by anchoring the needle within the envelope-embedded complex of the T3S secretome and - contrary to its counterpart in Salmonella - is not involved in substrate switching.

Resume Objectif Evaluer la conformite de la prise en charge therapeutique des enfants ayant eu une infection urinaire (IU) au protocole institutionnel du Centre hospitalier regional universitaire de Lille, dans le contexte d’augmentation des IU a enterobacteries productrices de beta-lactamases a spectre etendu (BLSE). Methodes Une etude observationnelle de pratiques, monocentrique, retrospective a ete menee sur un an (2010–2011). Les donnees de tous les enfants ayant eu une IU diagnostiquee au service d’accueil des urgences pediatriques ont ete etudiees. La conformite au protocole de la prise en charge initiale, puis apres la reception des resultats de l’examen cyto-bacteriologique des urines (ECBU) a ete analysee. Les facteurs associes a la non-conformite ont ete recherches. Resultats Trois cent quatre-vingt-treize enfants ont ete inclus ; une enterobacterie BLSE avait ete identifiee par 2,2 % des ECBU. La prise en charge initiale avait ete conforme au protocole pour 95 % des enfants et la prise en charge secondaire pour 80 %. La non-conformite etait due a un defaut de reajustement therapeutique dans 59 % des cas, et a une mauvaise indication de bi-antibiotherapie dans 20 %. Les facteurs associes a la non-conformite etaient, pour la prise en charge initiale, l’âge Conclusion La conformite au protocole avait globalement ete bonne mais pourrait etre optimisee en ameliorant la procedure de reevaluation apres reception de l’ECBU. Les IU a enterobacterie BLSE, encore rares dans ce centre, n’avaient pas ete source de non-conformite.

International audience; The synthesis of eight perylenediimide-based glycoclusters was readily performed from hexa- and tetra-propargylated cores through azide–alkyne “click” conjugation. Variations in the carbohydrate epitope (Glc, Gal, Man, Fuc) and the linker arm provided molecular diversity. Interactions with LecA and LecB, two proteins involved in the adhesion of Pseudomonas aeruginosa to host tissues, were evaluated by microcalorimetry (ITC). In both cases high affinities were obtained with Kd values in the nanomolar range. Further evaluation of their anti-adhesive properties using cultured epithelial cells demonstrated their potent anti-adhesive activities against Pseudomonas aeruginosa with only 30–40% residual adhesion observed. The fluorescence properties of the PDI core were then investigated by confocal microscopy on cell–bacteria cultures. However, the red fluorescence signal of the PDI-based glycocluster was too weak to provide significant data. The present study provides another type of anti-adhesive glycocluster against bacterial infection with a large aromatic PDI core.

Pseudomonas aeruginosa and Candida albicans are frequently coexisting opportunistic pathogens, responsible for colonization and infection in predisposed patients. They share a virulence specificity relying on auto-inducing, cell density-dependent molecules named quorum-sensing (QS). C. albicans virulence depends on its QS that influences morphological switch from yeast to filamentous form. Similarly, the production of P. aeruginosa virulence factors depends partly on QS molecules. Interactions have been investigated and demonstrated in vitro. P. aeruginosa may kill C. albicans either by producing toxins, such as pyocyanin, or by direct contact on its biofilm-dependent filamentous form. Cross-kingdom communication is a more subtle interaction: C. albicans can adapt its morphology in the presence of P. aeruginosa QS molecules, and inhibit P. aeruginosa QS-dependent virulence factor secretion, through farnesol, one of its QS molecule. But the in vivo relevance of these interactions is still controversial, as models of airway colonization/infection by C. albicans followed by subsequent P. aeruginosa pneumonia give contradictory results, suggesting the probable involvement of the immune system as a third party player. Finally, the authors of clinical studies performed in ventilated patients, indicate that C. albicans colonization could be a risk factor for P. aeruginosa pneumonia. The clinical outcome of C. albicans and P. aeruginosa interaction is uncertain, the virulence modulation demonstrated in these interactions opens new possibilities for future anti-infectious therapeutics.

Background Pseudomonas aeruginosa (Pa) is a Gram-negative bacteria frequently involved in healthcare-associated pneumonia with poor clinical outcome. To face the announced post-antibiotic era due to increasing resistance and lack of new antibiotics, new treatment strategies have to be developed. Immunomodulation of the host response involved in outcome could be an alternative therapeutic target in Pa-induced lung infection. Kynurenines are metabolites resulting from tryptophan catabolism and are known for their immunomodulatory properties. Pa catabolizes tryptophan through the kynurenine pathway. Interestingly, many host cells also possess the kynurenine pathway, whose metabolites are known to control immune system homeostasis. Thus, bacterial metabolites may interfere with the host’s immune response. However, the kynurenine pathway in Pa, including functional enzymes, types and amounts of secreted metabolites remains poorly known. Using liquid chromatography coupled to mass spectrometry and different strains of Pa, we determined types and levels of metabolites produced by Pa ex vivo in growth medium, and the relevance of this production in vivo in a murine model of acute lung injury. Results Ex vivo, Pa secretes clinically relevant kynurenine levels (μM to mM). Pa also secretes kynurenic acid and 3-OH-kynurenine, suggesting that the bacteria possess both a functional kynurenine aminotransferase and kynurenine monooxygenase. The bacterial kynurenine pathway is the major pathway leading to anthranilate production both ex vivo and in vivo. In the absence of the anthranilate pathway, the kynurenine pathway leads to kynurenic acid production. Conclusion Pa produces and secretes several metabolites of the kynurenine pathway. Here, we demonstrate the existence of new metabolic pathways leading to synthesis of bioactive molecules, kynurenic acid and 3-OH-kynurenine in Pa. The kynurenine pathway in Pa is critical to produce anthranilate, a crucial precursor of some Pa virulence factors. Metabolites (anthranilate, kynurenine, kynurenic acid) are produced at sustained levels both ex vivo and in vivo leading to a possible immunomodulatory interplay between bacteria and host. These data may imply that pulmonary infection with bacteria highly expressing the kynurenine pathway enzymes could influence the equilibrium of the host’s tryptophan metabolic pathway, known to be involved in the immune response to infection. Further studies are needed to explore the effects of these metabolic changes on the pathophysiology of Pa infection. Electronic supplementary material The online version of this article (doi:10.1186/s12866-016-0756-x) contains supplementary material, which is available to authorized users.

International audience; ObjectiveTwo years after the French guidelines, the objective was to assess the feasibility and efficiency of ultrasound-guided trans-vaginal drainage of tubo-ovarian abscesses (TOA) and to study the responsible germs.Material and methodsAll the patients with a larger abscess than 20 mm were included prospectively from May 2011 to July 2014 in the university hospital of Lille.ResultsSixty-nine drainages were performed among 50 patients. Success rate was 94%. No complication occurred. One germ was found in 55% of patients, the TOA was polymicrobian in 20% of cases.ConclusionUltrasound-guided trans-vaginal drainage of TOA is safe and effective with more than 90% of success rate.; ButNotre étude avait pour objectif d’évaluer, 2 ans après les nouvelles recommandations professionnelles, la faisabilité et l’efficacité des ponctions trans-vaginales écho-guidées dans la prise en charge des abcès tubo-ovariens (ATO) et d’étudier les germes responsables.Patientes et méthodesDe mai 2011 à juillet 2014, toutes les patientes présentant un abcès tubo-ovarien de plus de 20 mm ont été inclues de façon prospective, à l’hôpital Jeanne-de-Flandre du centre hospitalier régional universitaire de Lille.RésultatsSoixante-neuf ponctions ont été réalisées chez 50 patientes. Le taux de succès était de 94 %. Aucune complication n’a été observée. Un germe a été mis en évidence chez 55 % des patientes et l’ATO était polymicrobien dans 20 % des cas.ConclusionLe traitement des ATO par ponction trans-vaginale écho-guidée a un taux de succès supérieur à 90 % sans complication observée.

Background and objectives Infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) have become a major public health issue worldwide. Cefoxitin is a second-generation cephalosporin and is associated with a strong in vitro activity against ESBL. Patients and methods We conducted a prospective monocentric cohort study from 2012 to 2015 to evaluate the clinical efficacy and safety of cefoxitin in 15 patients treated for urinary tract infection (UTI) caused by ESBL-E, without any severity criteria. Results We included 15 patients; 11 were male patients with defined risk factors for ESBL-E. Ten patients presented with male UTI, three with pyelonephritis, and two with cystitis. Escherichia coli was the predominant pathogen. All patients had a positive outcome with a good tolerance (a skin rash without any sign of severity was observed in one patient). Microbiological cure was obtained in 9 patients out of 10 at the end of treatment. Conclusion Cefoxitin is an alternative treatment to carbapenems for urinary tract infections caused by ESBL-producing Enterobacteriaceae.

International audience; Bacterial vaginosis (BV) is considered as a trigger for an inflammatory response that could promote adverse pregnancy outcome (APO). We hypothesized that BV-related inflammation could be counterbalanced by anti-inflammatory and mucosal homeostatic responses that could participate in pregnancy outcomes.A total of 402 vaginal self-samples from pregnant women in their first trimester were screened by Nugent score. In this population, we enrolled 23 pregnant women with BV but without APO, 5 pregnant women with BV and developing APO, 21 pregnant women with intermediate flora, and 28 random control samples from pregnant women without BV or APO.BV without APO in pregnant women was associated with 28-fold interleukin-8, 5-fold interleukin-10, and 40-fold interleukin-22 increases in expression compared to controls. BV associated with APO in pregnant women shared 4-fold increase in tumor necrosis factor, 100-fold decrease in interleukin-10, and no variation in interleukin-22 expressions compared to controls. Next-generation sequencing of vaginal microbiota revealed a shift from obligate anaerobic bacteria dominance in BV without APO pregnant women to Lactobacillus dominance microbiota in BV with APO.Our results show that the anti-inflammatory and mucosal homeostatic responses to BV may determine outcome of pregnancy in the setting of BV possibly through effects on the vaginal microbiota.